Disease relevance of TNR

• By reverse transcriptase-polymerase chain reaction we have studied the existence of TN-R isoforms generated by pre-mRNA alternative splicing in various human astrocytomas and meningiomas [1].
• TNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL) [2].
• RESULTS: Compared with euthyroid control subjects, patients with hyperthyroidism had significantly elevated serum levels of IL-8 (506.8 pg/mL v. 7.0 pg/mL, p < 0.001) and TNR-alpha (18.6 pg/mL v. 8.7 pg/mL, p < 0.05) [3].
• In the present study the distribution of the inhibitory extracellular molecules tenascin-R (TN-R) and tenascin- C (TN-C) was examined by immunocytochemistry during evolution of the multiple sclerosis (MS) lesion, in which astrogliosis is a prominent feature [4].

High impact information on TNR

• The axonal recognition molecule F11 is a multifunctional protein: specific domains mediate interactions with Ng-CAM and restrictin [5].
• Furthermore, 2 molecules implicated in axonal pathfinding and mossy fiber sprouting, the extracellular matrix glycoprotein, tenascin-R (TN-R), and the hyaluronan receptor CD44, were increased in NBD hippocampal neuropil [6].
• Co-expression of TNR with T2N2 resulted in a mixed pattern of two conductance states, which is similar to that observed in wild-type CFTR [7].
• The deduced amino acid sequence of human TN-R (1358 amino acids) showed a homology to chicken and rat TN-R of 75 and 93%, respectively [1].
• Using DNA from a panel of human-hamster and human-mouse somatic cell hybrids and by fluorescence in situ hybridization, we have assigned the gene for human TN-R to the region 1q23-q24 [1].

Biological context of TNR

• Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1 [8].
• Circadian rhythm of the soluble p75 tumor necrosis factor (sTNF-R75) receptor in humans--a possible explanation for the circadian kinetics of TNR-alpha effects [9].
• Association of certain alleles and genotypes of the TNR/11q#1 repeat with both acute and chronic lymphocytic leukemia suggests the presence of a cancer related gene, involved in a wide spectrum of neoplasia, in the vicinity of this repeat [2].
• Association analysis was carried out for six single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (TNR, intron 1), covering the genomic ALDH5A1 sequence [10].
• The transcripts that were polymorphic in the TNR region were ATBF1-A (a homeodomain protein), clone 390013 on chromosome Xp11, a member of the family of the 14.3.3 protein kinase C regulators, a human translation initiation factor (an isolog of the yeast Suilisol gene 1), and a novel sequence (TR21) [11].

Anatomical context of TNR

• With regard to TN-R function in low vertebrates capable of CNS regeneration, questions of particular interest concern the (co)evolution of ligand-receptor pairs and cellular response mechanisms associated with axon growth inhibition and oligodendrocyte differentiation [12].
• Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth [8].
• Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size [8].
• These observations suggest that TN-R via its neuronal receptor contactin might induce a transition from long-distance growth of tectal interneurons to differentiation, including the formation of microprocesses [13].
• These data are analyzed with respect to our model of tissue organization that we term the "restrictin model of cell growth regulation." This model assumes a morphogen-like role of activin A in the hematopoietic system [14].

Associations of TNR with chemical compounds

• In a search for extracellular signals that affect the formation of microprocesses along neurites we found that the ECM glycoprotein tenascin-R (TN-R) but not other ECM glycoproteins increased the percentage of tectal neurons with actin-rich microprocesses and side branches [13].
• Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5) [15].
• TNR was correlated to the doses of histamine by an empirical equation [16].
• The expression of janusin is accelerated by exogenous testosterone [17].

Other interactions of TNR

• In contrast to TN-R-F3, TN-R-sulfatide interactions, mediating oligodendrocyte adhesion and differentiation, are highly conserved during vertebrate evolution [12].
• Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R [8].
• Using six HLM samples, the percentage total normalized rate (% TNR) was calculated to estimate the contribution of each P450 in the total metabolism of endosulfan-alpha [18].
• In multivariate analysis, a high alpha-fetoprotein level (risk ratio, 5.46; P = 0.003; risk ratio, 8.78; P = 0.006) and high TNR (risk ratio, 1.3; P = 0.03; risk ratio, 1.6; P = 0.02) were independent predictors of postoperative recurrence and overall survival [19].
• Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR) [20].

Analytical, diagnostic and therapeutic context of TNR

• The overall and disease-free survival rates in the high TNR (>/=2.0) group were significantly lower than in the low TNR (<2.0) group (P = 0.0001 and 0.0002) [19].
• To investigate the role of TNR/11q#1 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin [2].
• Five minutes before and five minutes after each challenge, TNR was determined by active anterior rhinomanometry [16].
• The bond strength of a high-impact, heat-cured denture base to three commercial brands of denture teeth, Bioform, Dentacryl, and TNR, was assessed [21].
• Group A comprised of government schools located in slum areas with an average parental income of INR (Indian National Rupees) 1050 per month and group B of elite private schools with an average family income of TNR 35,000 per month [22].

References